Many patients are suffering from diseases such as athlete's foot and candidiasis to be caused by fungi, and the diseases are difficult to be cured completely owing to repeated remissions and relapses. The number of female patients is showing an increasing trend along with women's participation in society in recent years. Thus, there is a social demand for an antifungal agent capable of treating the diseases in a simple manner.
It has been clarified that for a promising antifungal agent, a compound represented by the general formula (1) as a novel imidazole compound having an antifungal activity has an action of shortening a therapeutic period of diseases derived from fungi, and, in particular, luliconazole, which is an optically-active substance, can be exemplified (see JP 3278738 B). Further, such compounds are useful for onychomycosis, and a formulation for onychomycosis thereof is also already known (for example, see WO 03/105841). That is, the compound represented by the general formula (1) may be said to be a useful active ingredient that can be widely used for mycoses (has an antifungal action).

For mycoses, there are exemplified, in addition to visceral mycoses, mycoses to be caused by the growth of fungi on the skin such as tinea pedis, tinea corporis, tinea cruris, intertrigo, erosio interdigitalis blastomycetica, chromophytosis, and seborrheic dermatitis. In those diseases, it is desired that an antifungal agent for external use be directly applied to a disease site.
Further, in many antifungal agents, adverse effects such as hepatic dysfunction and renal dysfunction due to oral administration are observed in a certain percentage. In addition, in the case of oral administration, a drug is metabolized in the liver and the like by a first-pass effect and the like. Hence, the drug is administered in a large amount for the purpose of delivering the drug to a disease site at an effective concentration, resulting in a burden on organs such liver involved in metabolism. Accordingly, in the current aging society, the utilization of an antifungal agent for external use capable of avoiding the first-pass in the liver has a significant meaning in medical care because the antifungal agent places a small burden on an elderly person in weak physical condition and can be easily administrated.
Meanwhile, because the steric structure of a compound having an asymmetric carbon is unstable in a solution, the maintenance of the steric structure becomes a critical issue in addition to the solubility in the compound having an asymmetric carbon out of bulk drugs for antifungal agents, and thus, various studies are being conducted. This is because the steric structure may be easily changed in a dissolution state. Any of the addition of sugars (see JP 2000-169372 A) and the adjustment of a pH (see JP 06-065076 A) has been conducted as one measure for the above, for example. In addition, it is known that an imidazole derivative is easily dissolved by polyethylene glycol, to thereby provide satisfactory stability (see JP 05-070351 A). However, there is no definite law for maintenance property of such steric structure. Thus, it may be said that the case where the steric structure may be maintained is rare in itself. Further, such combination is incidentally found out under the present situation. In a formulation containing the compound represented by the general formula (1), there has been no finding about whether or not the maintenance of the steric structure of the compound becomes a problem, and further, it is not known how to achieve such maintenance of the steric structure. Under such backgrounds, in pharmaceutical administration and regulations, there is a demand for means for ensuring the stability suited for the compound represented by the general formula (1). In addition, an alcohol typified by ethanol and water are widely used medium ingredients in formulation. It is known that those ingredients may cause hydrolysis or the like to affect the stability of an active ingredient. However, there has been no finding that the ingredients have a preferred contribution to the stability in a specified mixing ratio.
Further, seborrheic dermatitis is exemplified as one of mycoses to which a skin agent for external use is suitable applied. However, a formulation used for seborrheic dermatitis is applied to a scalp site around the hair, and thus is used in a larger amount compared with that used for mycoses of the body and mycoses of the hands and feet. Therefore, the use of a solvent such as methyl ethyl ketone is restricted from the viewpoints of possibility of causing an irritation, flammability, and the like. Accordingly, there has been a demand for a formulation that is free of any adverse effect such as an irritation and can be easily administered. In addition, in order to ensure an effect, preferred is a form of a single-phase solution in which a drug is sufficiently dissolved in a formulation, and a drug is easily transferred to the skin. Because the compound represented by the general formula (1) is limited water solubility, one problem is how to prepare a formulation in a form of a single-phase solution without impairing the solubility.
In the case of developing a skin agent for external use to be used in medical care, a technology for allowing an active ingredient to be sufficiently absorbed in the skin is required as the most important technology. The skin has a defensive action against physical and chemical irritations from the outside. Thus, in general, the absorption amount of an active ingredient from the skin is slight. In order to overcome the problem, a method of improving the transdermal absorbability by various methods has been studied, and a method using a transdermal absorption promoter has been studied, for example (see JP 08-3070 A). For a method of improving the transdermal absorbability of an antifungal skin agent for external use, it has been known that the incorporation of ethylcellulose, water, and a plasticizer in a certain amount allows the antifungal skin agent for external use to be efficiently absorbed (see JP 07-223971 A). However, there is no finding on an effective method of improving the transdermal absorbability to develop the compound represented by the general formula (1) as the antifungal agent for external use. In particular, a method of maintaining the steric structure of the compound in a stable manner and improving the transdermal absorbability has not been studied in any way.